Malaria is a significant global health problem. It is widespread, and constitutes a growing health problem of major proportions, particularly in developing countries.
Malaria is caused by several species of the genus Plasmodium, the most virulent species being Plasmodium falciparum (P. falciparum). Parasites growing in erythrocytes are responsible for the pathological manifestations of the disease in man. During the blood stage of infection, P. falciparum parasites infect the cells and develop within the erythrocytes through three successive, morphologically distinct stages known as ring, trophozoites and schizonts. A mature schizont eventually produces multiple infectious particles, known as merozoites, which are released upon rupture of the red blood cells. The merozoites invade new red blood cells after a short extracellular life in the blood.
The increased resistance of the malaria parasite to drugs, as well as the resistance of the mosquito vector to insecticide, has increased the need for a malaria vaccine. H. S. Banyal and J. Inselburg, Am. J. Trop. Med. Hyg., 34(6): 1055-1064 (1985). One approach to the development of a vaccine has been to use monoclonal antibodies to identify and characterize specific malarial antigens involved in antibody-sensitive processes that are essential to the maintenance of the parasite growth cycle. These antibodies are known as "parasite inhibitory" antibodies. These parasite inhibitory antibodies can be induced by a host's immune response to the complementary antigens. Such an antigen, or combination of antigens, could therefore provide the basis for an effective malarial vaccine. Some parasite inhibitory antibodies have been isolated and the P. falciparum parasite antigens they recognize have been identified by H. S. Banyal and J. Inselburg, in Am. J. Trop. Med. Hyg., 34(6):1055-1064 (1985). See also, P. Deplace, et al., Molecular and Biochemical Parasitology, 23: 193-201 (1987); J. L. Weber, et al., Molecular Strategies of Parasitic Invasion, Agubian, Goodman and Nogueira (Eds.), Alan R. Liss, Inc., New York, N.Y. pp. 379-388 (1987); P. Deplace, et al., Molecular and Biochemical Parasitology, 17: 339-251 (1985); J. D. Chulay, et al., The Journal of Immunology, 139: 2768-2774 (1987); and A. Bhatia, et al., Am. J. Trop. Med., 36(1): 15-19(1987).
The key to developing an antimalarial vaccine based on a defined antigen is to isolate and characterize the gene encoding the antigen recognized by a parasite inhibitory antibody so it may be manipulated by gene cloning techniques to provide sufficient amounts of appropriate antigen for vaccine production.
Available approaches to diagnosing, preventing and treating malaria are limited in their effectiveness and must be improved if a solution is to be found for the important public health problem malaria represents worldwide.